The Neuropilin-1/PKC Axis Promotes Neuroendocrine Differentiation and Drug Resistance of Prostate Cancer - Université Paris-Est-Créteil-Val-de-Marne Access content directly
Journal Articles British Journal of Cancer Year : 2023

The Neuropilin-1/PKC Axis Promotes Neuroendocrine Differentiation and Drug Resistance of Prostate Cancer

Ariane Jolly
  • Function : Author
Fannie Semprez
  • Function : Author
Alexandre De
  • Function : Author
Arturo Londoño- Vallejo
  • Function : Author

Abstract

Background: Neuroendocrine prostate cancer (NEPC) is a multi-resistant variant of prostate cancer (PCa) that has become a major challenge in the clinics. Understanding neuroendocrine differentiation (NED) process at the molecular level is therefore critical to define therapeutic strategies that can prevent multi-drug resistance. Methods: Using RNA expression profiling and immunohistochemistry, we have identified and characterized a gene expression signature associated with the emergence of NED in a large PCa cohort including 169 hormone-naïve PCa (HNPC) and 48 castration-resistance PCa (CRPC) patients. In vitro and preclinical in vivo NED models were used to explore the cellular mechanism and to characterize the effects of castration on PCa progression. Results: We show for the first time that Neuropilin-1 (NRP1) is a key component of NED in PCa cells. NRP1 is upregulated in response to androgen deprivation therapies (ADT) and elicits cell survival through induction of the PKC pathway. Downmodulation of either NRP1 protein expression or PKC activation suppresses NED, prevents tumor evolution toward castration resistance and increases the efficacy of docetaxel-based chemotherapy in preclinical models in vivo. Conclusions: This study reveals the NRP1/PKC axis as a promising therapeutic target for the prevention of neuroendocrine castration-resistant variants of PCa and indicates NRP1 as an early transitional biomarker.
Fichier principal
Vignette du fichier
NRP1 manuscript-BJC.pdf (1.91 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03998379 , version 1 (15-12-2023)

Identifiers

Cite

Charly Blanc, Anissa Moktefi, Ariane Jolly, Pierre De La Grange, Denise Gay, et al.. The Neuropilin-1/PKC Axis Promotes Neuroendocrine Differentiation and Drug Resistance of Prostate Cancer. British Journal of Cancer, 2023, 15, ⟨10.1038/s41416-022-02114-9⟩. ⟨hal-03998379⟩
92 View
9 Download

Altmetric

Share

Gmail Facebook X LinkedIn More